Kidney Runner

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EAST MEETS WEST


ON KIDNEY FUNCTION


How the Kidneys are the Root of Wellness
in Chinese and Western Medicine.

With pesticides and herbicides as a primary additive to our food systems; water pollution being a global catastrophe showing no slowing down; regular alcohol consumption consistently promoted as a social norm; the prescription of pharmaceuticals as the primary tool for resolving a chronic pain epidemic: I think it’s fair to say that the general public in the U.S. is pretty oblivious to how important our kidneys are for maintaining the homeostasis of our bodies. Not only does it function as the filtration system for the bodies’ perpetual production of potentially toxic waste products, it produces some of our bodies’ most important regulatory molecules like glucocorticoids for the infamous flight-fight-fright response (cortisol, adrenaline/epinephrine, and norepinephrine), your reproductive hormones (including androgens), and aldosterone for regulating blood pressure, to name a few. These molecules also happen to function as both neurotransmitters and hormones — that means these molecular messengers can essentially interact with any organ system of the body. In Traditional Chinese Medicine, the kidney is more of a description of the interrelated capabilities involved with the actual two physical organs. TCM practitioners also consider the kidney system the root of the energetic storage house of the body (or the “ming men”). In the infographics below, I’ve tied in some of the interrelating biochemical functions described by our Western Medical System with key descriptions from Traditional Chinese Medicine. The goal is to better understand why our kidneys should be considered one of the most important organ systems for indicating an imbalance in our bodies. Hopefully, it will inspire you to better take care of your magnificent pair. -VF

“If the water of the kidney cannot control the fire of the heart, the mind-spirit will become restless.” 

The Renin-Angiotensin-Aldosterone System (RAAS) controls the blood pressure for fluid filtration and electrolyte balance through a network of checks-and-balances between the kidneys and the heart, though effects are experienced throughout the body. Hyperactivity of the RAAS system is also observed in depression.

“THE Kidney storeS Jing or the Essence of Life — the substance that nourishes, fuels, and cools the body.”

The characteristics of strong Jing include prominent facial features, hearing, teeth, hair, and strong adrenals/kidneys. These traits share the same embryological origin as neural crest cells (NCCs) — a stem cell population with great abilities of self-organisation that undergo challenging cellular migrations to form the associated structures. Jing is both inherited (genetics) and acquired (food/water).

“The Kidney is to dominate the regulation of Water Metabolism.”

The kidneys’ glomerular filtration removes excess fluid and waste products from the blood while playing a central role in the homeostasis of ions that are important for many biological functions (e.g. calcium, Vitamin D, etc.). 

“the kidney governs the bones, a substance born from water.”

The kidneys control the levels of calcium, Vitamin D/Calcitriol, phosphate, and cortisol, which are responsible for forming the crystalline structure of your bones. These compounds are also important for the regulation of central and peripheral mechanisms.

“The Kidney controls the reception and holding of the Qi to support the functions of the Lung.”

The regulation of acid-base equilibrium, modification of partial pressure of carbon dioxide and bicarbonate concentration, and the control of blood pressure and fluid homeostasis are all closely dependent on renal and pulmonary activities. 

 “The Kidney energy controls the sex drive and reproduction.”

Through the core energy center or “ming men”, the kidneys are depleted of “jing” during intercourse, and thus overexertion is warned against. We now understand that the kidneys are intimately connected to the adrenal glands, which release sex hormones (i.e. estrogen and testosterone) along with other neurohormones that regulate other functions like the stress response. The ovaries and testes also emerge from the primitive kidney during embryological development.

“The Spirit of the Kidney rules Willpower and the Survival Instinct.”

The kidneys produce many types of important hormones (histamine, serotonin, brain natriuretic peptide, adrenalin, norepinephrine, dopamine, etc.) that function universally as neurotransmitters, and are intimately connected with our state of being, our emotional and psychological health, and the seat of our primal state of fear.

I Gut A Feeling

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A GUT FEELING

FEAT. THE PAR2 IN YOU

The GI tract is the largest interface between you and the environment, and a primary influencer of your well-being, which is finally becoming increasingly understood as more research comes out (source). For the very first job that I landed fresh out of college, I was able to get my hands dirty (literally) in understanding the neurobiology of digestive disorders at a UCSF research lab (aka partaking in projects that required the dissection of mouse spinal cords and clearing of their intestines of poop). Oh the shit that I used to do… (cue punchline music*). Anyway, the founder of the lab had apparently done some major pioneering work on the role of this receptor, called Protease-activated Receptor 2 (PAR2 for short), in chronic pain associated with irritable bowel syndrome and inflammatory bowel disease. His team’s goal was to see if PAR2 could be exploited as a therapeutic target for chronic pain (source). Since then, I’ve developed a more holistic perspective on digestive health, but will always appreciate the impact of one problematic molecular mechanism on the whole. In homage to my time with digestive dysfunction, I’ve also created a karaoke video about the PAR2 in U in hopes of introducing an enjoyable way of learning about the science behind your well-being. -VF

An easy-to-digest overview of YOur Gut FEELINGS

SEROTONIN IS CONTROLLING

Besides being a critical processor of the nutritional requirements for this miraculous machinery we call our bodies, the human gastrointestinal system plays a major role in the “digestion” of your behavioral, emotional and physical capacities. This mechanism is monitored by a “second brain” which is officially known as the enteric nervous system (ENS): an expansive unit of over 500 million neurons (which is 0.5% the capacity of your brain and 5x that of the spinal cord), as well as a department of support cells. It relays information throughout your body from signaling pathways generated by but not limited to 30+ different cell types in the gut, molecules from digested nutrients (salts, fats, trace minerals, etc.), and the 100 trillion bacterial cells that support our digestion. Interconnected to the central nervous system (CNS) by the vagus nerve (and the lesser known prevertebral ganglia), the ENS lines the walls of the long tube of our gut, or alimentary canal, which measures about 30 feet end to end from the esophagus to the anus (source). Among one the critical communicators of the body, about 90% of the bodies’ serotonin reserves are manufactured by enterochromaffin (EC) cells in the gut with the support 2-6 pounds of bacterial flora, as discovered by a team at scientists at Caltech. Serotonin also regulates a whole entourage of biological processes including neurogenesis, cardiovascular function, intestinal motility, inflammation control, and bone mass accrual (source).

A BALANCING ACT

In Traditional Chinese Medicine, the organs, which aren’t delineated exactly the same as in Western anatomy, are responsible for regulating the whole spectrum of emotions that fluctuate throughout the day: the liver is the notorious wrangler of anger and frustration (most likely by filtering the blood of aggravating toxins); the energy center or “ming-men” of the kidneys monitors flare ups that cause fear in our hearts (which we now can partially prescribe to noradrenaline/adrenaline); our stomachs and pancreas process our worries in our immediate environments (by regulating blood sugar levels); and sadness is “digested’ by our lungs (ACE in regulating our blood pressure), skin (vitamin D for nervous system health) and large intestine (serotonin production). There’s also an additional non-physical digestive system called the triple burner residing over the head, chest, and thorax that controls all the organ relationships, and hence emotional balance — it is this heating system of the body/mind/spirit that regulates and distributes energy and water. Nowadays these functions can largely be attributed to the endocrine glands and hormonal distribution systems. It was also understood that the body maintains homeostasis (yin/yang) through processes that are analogous to the fundamental elements in our environment which, in general, are related to nutritional requirements (earth), power/organizational structure (metal), thermodynamics (fire), movement (water), and development (wood). How funny that practitioners have effectively applied this medical system for thousands of years without understanding the biochemical processes developed in Western Medicine, which have only gained traction over the last 200 years.

FOOD FOR FORM

One of the most overlooked aspects of the Western healthcare system is nutrition — in fact, most medical schools in the U.S. don’t even require their students to take a single nutrition course (source). In the ancient Indian medicine system of Ayurveda, health maintenance is entirely centered around nutrition, which include food, herbs and minerals (hence the culture’s delectable diversity of spiced delights). Prescriptions are made according to two main factors: your body makeup (prakruti), which consists of the distribution of three attributes (doshas), and six primary favours that support their functions. These three doshas, known as vata, pitta, and kapha, are correlated with the qualities of various biological energies that make up the body and mind. Interestingly enough, they have parallels with the mesomorph, ectomorph, and endomorph physiology defined in Western Medicine, which are influenced by the predominance of nervous tissue, bone mass, muscle, body fat percentage, rate of metabolism, etc. So it would make sense that specific foods would be more beneficial to someone with a tendency to gain weight (e.g. light salads that counteract the kapha dosha’s tendency for a sluggish metabolism) versus someone prone to weight loss and anxiety (e.g. sour foods for the vata dosha like oranges that contain vitamin C to promote healthy nervous system function). Your gut can even “taste” the macronutrient composition of the meal to trigger adequate responses for assimilating nutrients and eliminating waste products from your meals. Since Shirazi-Beechey’s pioneering work on the gut as a direct interface with the environment, researchers have found a specific distribution of receptors that detect sugars, fats, the amino acids (proteins), and bitter compounds in the GI tract — as well as all over the body including the lungs, CNS, testes, and skin (source). In fact, in Ayurveda clear skin is indicative of a healthy digestive system and overall balance of the body or three doshas (source).

ADDRESS THE STRESS

Normally a burst of cortisol is a healthy and necessary part of responding to a stressful situation through your ever-faithful fight-flight-freeze response. In fact this little glucocorticoid hormone has some major body-credentials that include: redistributing energy reserves like making your glutes more responsive to glucose (by thwarting the effect of insulin) when you’re running away from your problems; preventing you from passing out as that blood pressure ups the ante while you finally confront your demons; restrains any infected wounds from turning you into a swollen sack of flesh (for about 30 minutes) as a potent anti-inflammatory; and helps you selectively forget that the whole mess ever happened (memory consolidation). Your digestive system, on the other end, is curbed by the sympathetic nervous system for your “spidey senses” to operate at peak capacity — except for your liver which is on overdrive pumping out proteins to breakdown into glucose molecules for efficient fuel. All is well until stress becomes a chronic issue: it makes you grow a “beer belly” (from your brain’s cues to overeat and cortisol’s hand in fat cell production); you’re at a greater risk for Type II diabetes (from insulin resistance), a heart attack (constricted blood vessels), and autoimmune diseases (insulin resistance); your muscles start to waste away (dysregulation of the parasympathetic nervous system for nutrition processing); and you’re prone to a whole slew of mental health issues (e.g. insomnia, chronic fatigue syndrome, dementia, depression, etc.) (source).

The Role OF PAR2 in You

What is PAR2 and is it important in gastrointestinal health?

Protease-activated receptor 2 (PAR2), a receptor for inflammatory proteases, is a major mediator of neurogenic inflammation and pain. Injury and inflammation trigger the activation of proteases from the circulation, immune cells, and epithelial tissues that regulate cells by cleaving protease-activated receptors (PARs). Once activated, PARs regulate multiple pathophysiological processes, including inflammation, pain, homeostasis, and healing. PAR2 activation also promotes the central (brain, spinal cord) release of neuropeptides that activate second-order spinal neurons that transmit pain. These mechanisms contribute to painful inflammation of the intestine, pancreas, and joints (source).

How does PAR2 function on the molecular level?

PAR2 is a member of a family of four G protein-coupled receptors (GPCRs) - proteases released from injury and inflammation activate PAR2 on sensory nerve endings by cleaving it at specific sites within the extracellular N-terminal domains (outside of the cell). Proteases in circulation reveal tethered ligands that bind to and activate the cleaved receptors, such as the local release of these neuropeptides, which stimulate plasma extravasation (pus), infiltration of neutrophils, and vasodilation (neurogenic inflammation) (source).

What IS the role of PAR2 on the peripheral nervous system and skin?

Here is a brief video of the Principal Investigator (PI) that I used to work for at UCSF, Dr. Martin Steinhoff, briefly discussing how PAR2 also influences neuronal signaling and outgrowth in diseased skin. I shot this during the 2011 International Itch Conference in Japan, Tokyo which was organized by another scientific researcher I was working with at the time, Dr. Akihiko Ikoma.

A CLOSER LOOK at YOUR GUT LINING

The gut is far from a simple hollow tube — it’s full of cells that sense and respond to the contents, with ramifications for appetite, defense, and disease that researchers are just starting to uncover. This is an immunofluorescence stained cross-section of the lining of the small intestine that highlights the diversity of cells that constitute its structure: See the infographic “Protease-Activated Receptor (PAR2) Activation” that’s just below for a key to some the major cells found in the gut (and also pretty much throughout your body).

This is an immunofluorescence stained cross-section of the lining of the small intestine (image source).

THE CELLS IN YOUR GUT THAT carry PAR RECEPTORS

This is a summary of the pathophysiological effects of PAR agonists PAR1 and PAR2 are expressed by endothelial cells, epithelial cells, neurons, myocytes/smooth muscles, fibroblasts, and inflammatory cells. PARs trigger pathways related to inflammation, hyperalgesia, tissue repair and protection in these cell types.

Summary of the pathophysiological effects of PAR agonists PAR1 and PAR2.

I gut A feeling Feat. the par2 in u

As promised, here is the karaoke number on this multi-talented molecule that I've created in homage to my brief stint in GI research, but my lifelong respect for gut health. I used this research publication as a reference for the concepts and experiments conducted in PAR2 gut research, which was produced by a group of researchers that I used to work with. I’ve also included key below with definitions for the terms in the video that probably aren’t known by the typical lay-person. I hope you enjoy it!

P.S. This is not intended to downplay the importance of digestive diseases nor hurt anyone’s feelings — hopefully it will do the opposite, and maybe cause a slight cramp in your gut from a good guffaw.

KEY FOR "I Gut a Feelin’” Karaoke video

Basic Anatomy of the digestive system

Key for the basic identification of digestive organs for the "I Gut a Feelin’” karaoke video.

Cathepsin

“Catheptic activity” (derived from the Greek word kathépsein, meaning to digest or to boil down) was first described in the gastric juice during the 1920s. Cathepsins are now classified based on their structure and catalytic type - the one used in mice experiments referenced in the research publication that I mentioned, Cathepsin S (for Serine), was found to excite the neurons in the colon.

C-FOS/C-Fos Immunohistochemistry Staining

C-Fos is a proto-oncogene that is expressed as a protein c-fos in some neurons upon depolarization (activation). It can be detected by immunohistochemical staining on tissue, such as activated nociceptive neurons in the spinal cord. We commonly used this tool to see if there was a central nervous system response (i.e. spinal cord) from mouse experiments on the gut.

Chronic Colitis

Colitis refers to the inflammation of the inner lining of the colon, which can be caused by several conditions including infection, Crohn’s disease, allergic reactions, and can have painful ulcers.

Colonic Air Balloon

A colonic balloon is just as it sounds, and used as part of an experimental technique for creating visceral gut pain in mice.

Confocal scope/Confocal Microscopy

Confocal microscopy is a type of microscopic imaging that uses lasers programmed to focus on a specific plane of tissue that’s been labeled with immunofluorescent markers. It’s used to create pretty, magnified images like the one included above.

Crohn’s/Crohn’s disease

Crohn’s disease is an inflammatory bowel disease that can cause severe abdominal pain, severe diarrhea, fatigue, weight loss, and malnutrition. I don’t have Crohn’s (as conveniently compatible with the lyrics), but I have known one person who’s successfully managed his symptoms with a combination of medications, vitamins, diet, exercise, and medicinal marijuana.

Gallstones

Gallstones are hardened deposits of the digestive bile, that can form within the gallbladder. They can cause pain, nausea, and vomiting if they block the ducts of the gallbladder on their way out. This is a more common condition in patients with Crohn’s disease.

MPO/Myeloperoxidase Assay

Myeloperoxidase (MPO) is a peroxidase enzyme found the most in neutrophil granulocytes (a type of white blood cell ) — basically in the presence of pus released during inflammation. Think about the times you used hydrogen peroxide to disinfect a scrape. The peroxidase in blood, cells, bacteria that break down the H2O2 into water and oxygen (which is responsible for the disinfectant properties against some bacterial strains).

The Abnormal Psychology of Kurt Cobain

For a class on Abnormal Psychology that I took well over a decade ago, and there was an assignment that helped clarify a situation in my family, and ultimately helped me make peace with it. I had to conduct a mental diagnosis on a public figure known to have had a mental disorder using criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM–5). Although it’s not a professional diagnosis, the core content is still relevant in understanding how mental disorders can develop and progress as a consequence of both external and inherited factors. And possibly to question the use of medication for regulating what society considers "abnormal behavior.” -VF

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A Mental Diagnosis of Kurt Donald Cobain

Introduction:

Kurt Donald Cobain was the lead singer, songwriter, and guitarist of the Seattle-based band Nirvana that went down in rock music history as a supernova influence in popularising what would become known as “grunge music.” Nirvana’s most recognized hits can still be heard over mainstream media, which include “Smells like Teen Spirit,” “Come As You Are,” and the controversial “Rape Me.” Cobain’s torturous lyrics and melancholiac tunes redefined music; the arrival of his band’s hit albums marked a dramatic shift from the more hip-hop/pop genres during the ’80s and '90s music culture. However, he never adjusted to the enormous success and eventually took his life in 1994 at the young age of 27 — only three years after the release of his major-label debut album, Nevermind. Although Cobain’s death is often attributed to his unhappiness of having gone from proud indie-rock rebel to mainstream superstar, he also had a life-long struggle with mental illness and drug abuse. An initial observation of his death suggests that he lived the typified short, extreme and jaded life typical of many famous artists and musicians. However, further examination reveals the tragic circumstances that lead to his suicide and the story of an extraordinary person that was extinguished too soon by his insufferable pain (4).

Background:

Cobain’s Early Life

On February 20, 1967, in Aberdeen, Washington, Cobain was born to Don and Wendy Cobain. Based on most accounts, Kurt’s early life appeared to be happy and his family seemed like any other all-American family. He was, however, a particularly hyperactive child who began developing an interest in music early on in life. According to interviews, his Aunt Mari recounted the charismatic child that Kurt had been: “He was singing from the time he was two... He had a lot of charisma from a very young age.” However, his hyperactive behavior entailed tactics like diving off the rooftop of his childhood house onto a seemingly safe pile of blankets and pillows. This imaginative seven-year-old had dreams of becoming a stuntman like his idol stunt performer "Evel Knievel.” Around this time, Kurt was diagnosed with Attention-Deficient Hyperactivity Disorder (ADHD) and was put on Ritalin shortly after (3).

Baby Kurt Cobain (source).

Divorce and Depression

Cobain’s life took a dramatic turn when his parents divorced in 1975 when he was about eight years old. His mother recalled how he took the divorce very seriously and became increasingly withdrawn and defiant. In a 1993 interview, he described the torment he felt about the divorce: “I remember feeling ashamed, for some reason. I was ashamed of my parents. I couldn’t face some of my friends at school anymore, because I desperately wanted to have the classic, you know, typical family. Mother, father. I wanted that security, so I resented my parents for quite a few years because of that.” Unfortunately, both his parents were often infuriated with Cobain’s rebellious behavior, so he often found himself shuffled between friends and extended family members. During this period, Kurt was reportedly diagnosed with Bipolar disorder — it has the same characteristics as major clinical depression, but with manic mood swings. As Kurt undoubtedly knew, his bipolar illness would become increasingly difficult to manage (3).

“I remember feeling ashamed, for some reason. I was ashamed of my parents. I couldn’t face some of my friends at school anymore, because I desperately wanted to have the classic, you know, typical family. Mother, father. I wanted that security, so I resented my parents for quite a few years because of that.”
— Kurt Cobain on his parents' divorce, 1993 Interview

Cobain’s Adolescent Years

Cobain’s teenage years were even more difficult as his home and school life became increasingly toxic. At school, he was a social outcast who took no interest in getting involved with the typical social scene and extracurricular activities. Despite his lack of interest in sports, he would eventually join and excel in the junior high wrestling team at his father’s insistence. The only academic subject he focused on was his art courses, and he often could be found drawing in class, especially of images affiliated with fetuses and human anatomy. He frequently was an easy target to bullies at school because of his frail stature and for befriending a gay student. And he would often be accused of being gay himself because of the friendship, but he would later admit that he was not but wished he was just to “piss off homophobes.” Unfortunately, at the time, homophobia was particularly prevalent when the US was experiencing the height of the HIV/AIDS crisis with infected individuals predominantly from the gay community (3).

Kurt Cobain's police mug shot from May 1986 (source).

Kurt engaged in his fair share of mischievous behavior that often got him into trouble with the law. It has been noted that in interviews Cobain claimed that he used to spray paint “God is Gay” on pickup trucks around Aberdeen, and was once arrested for spraying another derogatory message. Regardless of the struggles that he endured during his childhood, Cobain maintained strong morals against prejudice. He once said during a performance: “At this point, I have a request for our fans. If any of you in any way hate homosexuals, people of a different color, or women, please do this one favor for us — leave us the fuck alone! Don’t come to our shows and don’t buy our records” (4).

“At this point, I have a request for our fans. If any of you in any way hate homosexuals, people of a different color, or women, please do this one favor for us — leave us the fuck alone! Don’t come to our shows and don’t buy our records.”
— Kurt Cobain, 1991

Family Matters

According to an interview with Cobain’s cousin, Beverly Cobain, suicide and alcohol abuse were prevalent among members of the Cobain's which often tore families apart: “Alcoholism runs rampant in the Cobain family. When I was growing up there was always alcohol and violence in our home. This was also true in Kurt’s home, so it isn’t’ surprising that he would turn to alcohol and other drugs to ease any kind of discomfort. It’s my observation that the Cobain men had painfully low self-esteem and used alcohol to relieve their inhibitions, to feel like they thought everyone else felt. So who would Kurt have had as a role model for healthy behavior and self-esteem? Where could he turn to feel good about himself?” In her account on his suicide, she had stated: “The first two suicides were also Cobain males: my father’s brothers, both with guns” (2). Based on his family history, it’s highly likely that his maladjusted behavior was a consequence of childhood abuse and neglect, inadequate parenting, as well as a genetic predisposition to depression.

Cobain decided to drop out of high school two weeks before graduation day, realizing that he wouldn’t have enough credits to graduate anyway, and was repelled by the idea of staying any longer. His mother, unable to deal with him any longer, gave him an ultimatum to either get a job or leave. Soon after, young Kurt found his belongings packed away in boxes and kicked out of his mother’s home. He would often stay at a friend’s house and occasionally sneak into his mother’s basement. He worked odd jobs and would earn just enough to rent out an apartment with a friend starting in June 1985. In late 1986, he was able to save enough money to live alone in a house that he rented (3).

Nirvana's Kurt Cobain Credit: Getty (source).

Passion for Music

Music was one of the few things that Kurt found an escape from his problems. Unlike every other teenager at the time who was listening to the latest pop hits over at the local diner, Cobain would often run off to attend punk shows in Seattle, which at the time was a hot spot for a thriving Pacific Northwest punk scene. Later on, he would make frequent trips out to Olympia, Washington to attend rock shows, and write his music with the guitar that his uncle had given him for his 14th birthday. Later in his high school days, he would meet fellow punk-rock fanatic Krist Novoselic who’d eventually agree to collaborate with young Cobain. In 1986, Cobain and Novoselic moved to Olympia and formed what would become the superstar rock band Nirvana. It initially featured drummer Chad Channing, who would be replaced by Dave Grohl in 1990. By 1988, Nirvana was performing their signature sound that would be later labeled “grunge” in that region. In 1989, the band recorded their first album Bleach under a Seattle-based independent label Sub Pop. By 1991, they signed with Geffen Records and released their breakout album Nevermind, launching their success worldwide and earning them a reported $550 million in the U.S. alone (4).

Love on the Mind

Music was not the only thing on Cobain’s mind. In 1989, Cobain met Courtney Love for the first time at a concert, who was also the lead singer of her own band, Hole. After finding out from Cobain’s bandmate Grohl that they had mutual crushes, Love began to pursue Cobain after more than a year since their first meeting. On February 24, 1992, a few days after Nirvana’s Australian tour concluded, Cobain married Love on Waikiki Beach in Hawaii who was also pregnant at the time with their first child. On August 18, 1992, the couple gave birth to their only daughter, Frances Bean Cobain.

Regardless of the welcoming of their new bundle of joy, their love never was a fairy tale story. They were both notorious heroin addicts who often bonded over drug and alcohol binges. Love admitted in a 1992 interview published in Vanity Fair to have been using heroin while (unknowingly) pregnant. Needless to say, their romance attracted a significant amount of media attention, and the couple was constantly hounded by tabloid reporters. Cobain’s fans would often accuse Love for riding on the coattails of Cobain’s success and for marrying him just to promote her band. Their reputation would become so notorious that Child Welfare Services would launch an investigation on the couple’s fitness as parents; the case was eventually dismissed due to the lack of legal leverage (4).

Kurt Cobain and Frances Bean Cobain (source).

Drug Addiction and Interventions

The pressure of fame was just one of the multiple factors that aggravated Cobain’s drug addiction. Throughout most of his life, Cobain struggled with depression (bipolar disorder), chronic bronchitis, and intense physical pain caused by a chronic stomach condition. Doctors were not able to pinpoint the source of his physical ailments, so Cobain often opted to self-medicate with heroin to numb the painful stomach ulcer and irritable colon. He had his first hit in the late 90s and like many, became a full-fledged addict within months. His addiction also began to put stress on his relationship with his fellow bandmates. During their promotional tour for Nevermind, he would pass out during photo shoots and appear sunken-eyed during performances, indicating that he had shot up earlier that evening.

In early 1993, Cobain made his first attempt at rehab; but after he leaving, he would appear gaunt and pale, and suffered from withdrawal symptoms. Not long after, Cobain’s addiction resurfaced. In fact, in July 1993, he suffered another drug overdose just hours before a performance at the New Music Seminar in New York. Instead of calling an ambulance like any other concerned person, Love would inject Cobain with a dose of illegally obtained NARCAN® (naloxone HCl) to bring him out of his unconscious state. Cobain, amazingly enough, would proceed to perform with his band without the audience noticing anything out of the ordinary (3).

Death by Suicide

Cobain’s supposedly first attempt or at least reported attempt at suicide occurred on March 6, 1995, when he overdosed on a lethal combination of the drug Rohypnol and alcohol in his Rome hotel room. Once he returned home, friends and family staged an intervention, and he eventually agreed to check into rehab. However, a few days after arriving, Cobain’s nurses said he would ask to go out to smoke but would leave the facilities by jumping over the walls. He pretty much fell off the radar after taking the next flight back to Seattle. Most of his friends did not how about his whereabouts, and eventually, Love was pushed into filling a missing-persons report and hiring a private investigator, Tom Grant, to find him.

On April 8, 1994, Cobain’s body was discovered in a spare room in his Seattle home by electrician, Gary Smith, who was sent to install security lighting at the time he saw the body. The autopsy report concluded that his death was a result of a “self-inflicted shotgun wound to the head.” The gunshot blast destroyed his head so badly that it was beyond recognition; his body would later be officially identified by his fingerprints. He left behind a suicide note where he addressed his wife Love, his daughter, as well as many of his fans. A toxicology report would later confirm extraordinarily high levels of heroin in his system. And it was estimated that his death was on April 5, 1994. Thousands of fans would attend his funeral and even more mourned his death (4).

The portion of Cobain’s suicide note that addresses his loved ones (source).

Cobain’s Abnormal Behaviour

Attention disorder

As a child, Cobain was diagnosed with Attention Deficit Hyperactive Disorder (ADHD) primarily after pulling dangerous stunts like jumping off rooftops in imitation of Hollywood stunt actors. And apparently, he was often “distracted” and “spoke rapidly.” Consequently, he would be put on Ritalin (methylphenidate) which is a central nervous system stimulant that is clinically reported to produce side-effects including difficulty sleeping, nausea, headaches, lack of hunger (leading to weight loss) and dry mouth. Even though Cobain presented symptoms of clinical ADHD, his behavior as a child may not have necessarily been deemed abnormal or “hyperactive'“ if it hadn’t entailed potentially dangerous consequences or if he was raised in a different environment, which I’ll elaborate on.

Medicated Discipline

Better use of discernment for managing a child’s energetic behavior could have included educating him on the reality of the stunts performed by professional actors, and to provide a safer outlet such as supervised gymnastic classes. The child’s behavior could have at least been curbed to safer limits without the use of brain chemistry-altering medications. But his family also had a history of maladjusted behavioral patterns like alcoholism and poor parenting that probably derailed more productive courses of action. His behavior may have been managed differently if he were raised in a non-western cultural background with alternative standards. For example, the Maasai (East African pastoralists) require all males to kill a lion single-handedly as part of a rite of passage to becoming a Moran — an elite group of young warriors and defenders of the community and its livestock. But in a traditional Asian household, you would have “normally” been disciplined into submission by your primary caretaker, as a psychiatric intervention is generally considered “excessive.”

Brain scans of ADHD subjects (red) vs control subjects (yellow) showing distribution of brain activity: ADHD subjects showed additional unique subcortical activations that included thalamus, brainstem, cerebellum, and hippocampus (source).

The Social Outcast

There often appears to be a common thread among people who display behaviors outside of societal norms to have experienced ridicule from their peers for being “abnormal.” Cobain was considered an oddball among his peers for not being a stereotypical hyper-masculine American teenage boy: he disliked sports; listened to and attended rock concerts; and preferred solitary confinement in his room. However, some of his outright delinquent antics are still considered problematic and illegal by today’s standards, such as spray-painting public property with profanity. At school, he was an easy target to bullies for being “awkward” and “meek”, and for befriending an openly gay student. Homophobia was especially taboo back in the '80s and '90s when the HIV/AIDS epidemic was at its peak and homosexuality was falsely associated as a cause. Traditionally, the acceptance of homosexuality is more prevalent in Asian cultures and even considered to be holy by some religions. Nonetheless, his depressed behavior and general disdain towards society could have been attributed to the abuse he endured by his peers (4).

Genetic vs Environment

Cobain may have had a genetic predisposition to bipolar disorder and drug addictions, but environmental cues often initiate and enforce these disorders. As accounted by his cousin, many members of Cobain’s family, predominantly the males, suffered from depression, alcohol abuse, and drug addictions. However, there were uncontrollable factors in his home environment that could be attributed to his mental breakdown. After his parents divorced, he never truly had a stable family environment. Both his parents would remarry, and his father reportedly spent more time raising his new family which further added to Cobain’s resentment. Neither of his parents wanted to deal with a difficult child and he was frequently shuffled between family and friends; his mother would eventually kick me out of the house. Needless to say, his anger and rebellious behavior were a reflection of how he felt towards his parents for not giving him the love and attention that any child needs to thrive. To add fuel to the pain, Cobain’s initial addiction to heroin was a way to ease stomach ulcers, which may have even been a side-effect of the Ritalin he was forced to take as a child, as well as the buildup of stress caused by all fronts of his life.

Research Article on how suicide may be predicted by epigenetic model (source).

The Tour Life

In his later years, his music production and touring schedule was often rigorous and overwhelming. People with strong social networks and support systems are better able to cope with stress. However, it did not help that Cobain’s immediate support network also lived the same drug-fueled, sexually promiscuous lifestyle that was typical of the music business during that era. "Regular” people often have lower rates of drug abuse due to the lack of resources; heroin, cocaine, and other Schedule 1 narcotics are more prevalent in the social circles of the rich and famous. To that subculture, drug abuse had been (and may still be) almost normal and expected, which Grohl has verified in an interview as a non-user himself. Once Cobain was addicted, however, he began to lose touch with his immediate circle as well as his music, which increased his stress levels, as well as his feelings of loneliness and helplessness (4).

Suicide Ties

It is well known that this music legend died by suicide. Suicide still ranks among the top ten leading causes of death in Western countries; it ranks as the third most common cause of death in the United States for 15 to 24-year-olds. Males are more likely to perform successful suicides using violent methods like gunshot blasts to the head. There is also a fair amount of evidence that genetic factors play a role in suicide. There were two other suicides in Cobain’s family, both being males. Studies have also shown a higher concordance rate of suicide between identical twins in comparison to more distant family members. Also, sociocultural factors have a significant influence — Whites/Caucasians have a higher rate of suicide than African Americans, though most European countries have among the lowest suicide rates. Nonetheless, suicide is still considered abnormal and condemned by the general population (1).

DSM IV Diagnostic Criteria of Bipolar Disorder 1 & 2.

DSM-IV Full Diagnosis of Kurt cobain

Axis 1: Bipolar disorder

This mood disorder is characterized by the occurrence of Major Depressive Episodes and at least one Manic Episode or Mixed Episode (not induced by drugs or another general medical condition).

DSM Criteria for Major Depressive Episode:

(A) To be considered as a major depressive episode, a person must have at least five DSM-indicated symptoms during the same 2-week period and represent a change from a normal predisposition.

(B) At least one of them must be either: (1) a depressed mood or (2) a loss of interest or pleasure (5).

  1. Cobain showed depressed and irritable moods that were confirmed by a personal report of sadness and emptiness and by observations of others. There were dramatic reports that Cobain would spend months binge drinking and engaging in violent behavior like vandalizing property or engaging in fights with fans who he felt were an insult to his music. His cousin, Beverly Cobain, confirmed that he was diagnosed at a young age with Attention Deficit Hyperactive Disorder [ADHD], and then later with bipolar disorder. She said he often had mood swings where he would be complacent at one moment and then angry, irritable, and distracted the next moment (2). His song lyrics, like the one song ”Rape Me,” “I Hate Myself,” and “I want to Die” reflected his anger and mental dysfunction (3).

  2. He showed “markedly diminished interest or pleasure in all, or almost all, activities of the day, nearly every day.” He often felt overwhelmed by the success of his band and the demands that came with it, often feeling disinterested in performing with his band. His widow would later report how desperately unhappy Cobain was with the group; he would say to her, “I hate it. I can’t play with them anymore.” For years, Cobain would often end his concerts by smashing his guitar and amplifier and become wildly angry at the drums and the audience (3).

  3. He also showed significant weight loss (by DSM standards, a change of more than 5% of body weight in a month) as well as fatigue and decreased appetite. Fans said Cobain often appeared gaunt with painfully sunken eyes during concert performances — this was also attributed to his heroin addiction and withdrawal symptoms when he tried to quit. Reportedly, he was considered borderline anorexic and basically would live off only booze and heroin for months on end (4).

  4. Throughout his life, Cobain suffered from insomnia nearly every day. Cobain would often not sleep for days on end. He often tried to self medicate himself with heavy doses of heroin, excessive alcohol drinking to numb his mind enough to sleep (4).

  5. Cobain was often haunted by feelings of “worthlessness or excessive or inappropriate guilt” (which may have been delusional) nearly every day (not merely self-reproach or guilt about being sick). Throughout his life, Cobain often said he had these constant feelings of “helplessness” and “utter despair”, which may have been triggered by the traumatizing event of his parents’ divorce. According to sources, a Seattle artist once made an observation: “The two things about Kurt were that he always thought of himself as the injured party, and he never spoke his mind.” Cobain would also often describe himself as “ugly, awkward, uptight, and socially retarded” (4).

  6. Most notably, Cobain had recurrent thoughts of death and often contemplated suicide. There are two documented records of attempted suicide, one of which successfully ended his life. His first attempt involved an overdose involving a potent combination of alcohol and Rohypnol, which is a powerful sedative that depresses the central nervous system. His second, and final attempt, was when he fired a shotgun into his mouth while intoxicated, instantly causing death upon impact.

The DSM-IV Criteria for a Manic Episode must include:

(A) A distinct period of abnormally and persistently elevated, expansive, or irritable mood that lasts for at least 1 week.

(B) During this period of emotional disturbance, a person must show a significant degree of at least three of the DSM-specified symptoms (5).

  1. During his manic periods, Cobain showed “inflated self-esteem or grandiosity.” It was reported that Cobain was especially upbeat and confident during a specific period of his touring season. According to disc jockey Marco Collins: “He was in a different world, but he was happy. Whatever demons caught with Kurt, they weren’t there in early January” (4). He may also have had Seasonal affective disorder (SAD).

  2. He also was more talkative than usual or felt the pressure to keep talking. Unlike his alternate gaunt and depressed persona, taking place on stage during his manic episodes was a charismatic performer. He would casually lit a cigarette and talk to the audience, expressing how much he loved everyone. Cobain was also “unassuming, genial” and even eager to meet the photographers during his New Year’s concert (4).

  3. His creative ability was fuelled during his manic periods, where he’d have a “flight of ideas or subjective experience [characterized] by racing thoughts.” He was the band’s initiator of ideas and wrote the majority of the lyrics and tunes to the band’s hit albums (4).

  4. Cobain also showed “excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments).” Cobain often engaged in destructive drug binges and random sexual encounters that often involved multiple parties. One visitor described Cobain as “wild… a virtual lunatic.” According to Frank Hule, “Kurt was doing $100-a-day of heroin, chasing it down with cough syrup, and falling asleep with a lit cigarette in his mouth” (4).

Axis II: UNAssociated AXIS 1 disorders

Cobain did not have a personality disorder that is not associated with AXIS I disorders.

Axis III: General Medical Conditions

Throughout most of his life, Cobain suffered from chronic bronchitis, a nagging stomach ulcer and irritable colon, and depression. The gastric disorder was so debilitating that it eventually took a toll on his emotional stability. Doctors would never be able to pinpoint the cause of the pain; they guessed it was caused by his childhood scoliosis or by the stresses of his music career. Consequently, doctors were not able to provide him with sufficient treatment or medication. Cobain often opted to self-medicate with high doses of heroin to numb out the gastric pain. As his heroin addiction progressed, he developed more chronic medical conditions associated with the side-effects of heroin abuse: nausea and vomiting, depressed respiration, clouded mental functioning, collapsed veins, and bacterial infections.

AXIS IV: Psychosocial and Environmental Events

Cobain’s insecurities and depression may have been triggered by his parents’ divorce. After his parents separated, Cobain’s childhood was very unstable; he constantly moved between his parents, family members, and friends. Eventually, Cobain was kicked out by his mother, and he often lived with friends Throughout his adolescent years, he was considered to be a loner and often was an easy target to bullies. As an adult, he had many friends that he met through the music industry and a huge fan base, but his primary support group generally consisted of his wife and daughter. However, his wife was often just as high or drunk as he was. Their unstable lifestyle fuelled by drugs and alcohol led to marital problems; the couple was often found at each other's throats. Their home was frequently described as empty and depressing; the walls had no pictures since the couple did not stay at one place long enough to establish a solid foundation. During his musical career, Cobain was surrounded by a fast-paced environment full of drug abuse and sexual promiscuity. Due to these factors in combination with the stresses and demands of performing, Cobain often felt emotionally alone and physically drained.

AXIS V: Global Assessment of Function (GAF)

Cobain was at high risk of hurting himself by serious suicidal act with the expectation of death.

References:

(1) Butcher, J.N. Mineka, S. Hooley, J.M… 2005, Abnormal Psychology Twelfth ed. Boston: Pearson Education, Inc.

(2) Libby, B.. 2002. Special Report: Even in his Youth. Retrieved May 28, 2008, from Blue Cross Blue Shield of Massachusetts. Website: Source.

(3) Martin, M.. 2005. Kurt Cobain. Minnesota: Capstone Press.

(4) Standford, C.. 2004. Kurt Cobain. New York: Carroll & Graf Publishers.

(5) Fleener, P.E. 2006. DSM IV: Bipolar Disorder I. Retrieved May 28, 2007, From Mental Health Today. Website: Source.

Original Copy with additional discussion topics on mental disorders

The Tale of Count DRAK2

DRAK2 was a molecule that I conducted research on back in a UCI laboratory for the Department of Immunology. And at the time I picked it because it sounded cool and somehow reminded me of Dracula, but I didn't think too much of it because it seemed like a silly idea. But after some reflecting on this real-life death-inducing molecule, I've come to realize that the founder of DRAK2 and probably everyone in my lab was already in on the pun. So here's my ancient recount on the tale of DRAK2. Oh, and read to the end for a bonus addition of my personal encounter with Count Dracula (cue maniacal laugh*). -VF

DRAK2 TRANSLOCATES IN T-CELLS (& B-CELLS)

T-cells possess the means to kill infected cells, and if not properly regulated, they can cause uncontrollable damage to normal, healthy cells, resulting in autoimmune disorders (source). DRAK2 is such an immunoregulatory molecule that negatively regulates T-cells and B-cells (like a chaperone), and is especially operative in developing and mature lymphocytes (source).

FREAKY FACT: Although Bram Stoker's Gothic novel Dracula popularised the idea of vampires being mythical creatures from Transylvania, the greatest number of real tombs with impaled corpses (about 100 found) assumed have been considered vampires were found in Bulgaria (source).

Death-Associated Protein Kinase 4 Family

Though DRAK2 is a serine/threonine kinase that’s a member of the (DAPk)4 family that possess abilities to potentiate apoptosis, DRAK2 serves as a mediator to a multitude of cell-death signaling pathways. As a negative regulator, DRAK2 sets the sensitivity of naïve T-cell activation. Defects can lead to disorders that include cancer, neurodegenerative diseases, and autoimmune diseases (source).

FREAKY FACT: Bram Stoker’s 1897 novel also portrays the fears and anxieties of Victorian society during the Industrial Revolution when the advent of new technologies caused shifts in women's choices to work, in sexual freedom, increased oversight in science research, etc. (source).

UV Radiation Exposure Triggers DRAK2

In light of death signals, one of the extracellular stimuli that induce DRAK2 to initiate apoptosis so happens to be UV irradiation (the others being protein molecules like Interleukin-2) (source). As an infamous culprit to skin cancer, UV light can also directly cause cell death by breaking double-stranded DNA and activating other signaling molecules that regulate cell survival (source). 

FREAKY FACT: There's a very rare disease called porphyria (also called the "vampire" or "Dracula" disease) that causes vampire-like symptoms, such as  extreme skin blistering upon exposure to sunlight, reduced number of red blood cell count, and sometimes hairiness (source).

Autophosphorylation of DRAK2

To activate the kinase, DRAK2 goes through a transformational modification of its protein structure that involves a process of auto- (selfie) and trans- (groupie) phosphorylation (source). Upon stimulation, the kinase catalyzes this phosphorylation reaction on its active site with the inception of a phosphate most commonly from ATP, the cell’s energy currency (source).

FREAKY FACT: Though capes were a real trend during the 1800s, they are innately magical - its etymology has the same root as “escape,” as in “to get away.” In other words, it bestows one power to evade problematic circumstances, making Dracula or any wearer quite the formidable foe (source).

DRAK2 TRANSLOCATES INTO THE NUCLEUS

Once activated, DRAK2 translocates and accumulates in the nucleus with the help of a built-in honing mechanism known as the nuclear-localization signal (NLS) sequence, and awaits further notice (source). A factor in the nucleus, which is likely the ultimate target of DRAK2 phosphorylation, may corroborate with other effectors to transduce the apoptotic signal of DRAK2 (source).

FREAKY FACT: During medieval Europe, villagers blamed vampires for unexplainable misfortunes like a bad harvest. When they unearthed graves to check, the bodies would pop up with seemingly fresh blood from their mouths, which was unknowingly caused by a delayed intestinal putrefaction process (source).

DRAK2 Recruits the Final Executors

Based on its structure, DRAK2 is unlikely to possess the protease-type abilities that actively breakdowns cells, but may instead work as an agent that transfers apoptotic signals into the nucleus. However, several other proteins are translocated into the nucleus along with DRAK2, many of which have the DNase or protease actions that can work as effectors in the execution of apoptosis (source). 

FREAKY FACT: The real-life muse behind Dracula, Vlad III or Prince of Wallachia, consolidated his power by inviting hundreds of feuding boyars to a banquet, and would stab his unknowing guests before impaling their still-twitching bodies. Through various methods, he has killed ~80,000 people (source).

DRAK2-/- Cells ARE more sensitive to STIMULI

While its abnormal expression induces death, oddly enough there’s no difference in mice missing the molecule entirely (DRAK2−/−) unless exposed to a toxin like SEB; then, mass T-cell death ensues (source). The paradox of DRAK2−/− being resistant to autoimmune disorder yet possesses hyperactive T-cells suggests that DRAK2 promotes the survival of T-cells during clonal expansion (source).

FREAKY FACT: In 2012 the Municipal Council of Zarozje issued a public health warning to residents, instructing them to place garlic and holy crosses around their homes. The reason: Sava Savanovic, Serbia’s most notorious vampire, was apparently on the loose (source).

DRAK2 negatively regulates Ca2+

The primary way DRAK2 maintains control of T-cell activation is by negatively regulating calcium mobilisation, which is also critical for the balance between life and death for many cell types. Without DRAK2 signaling, T-cells require greater tonic signaling for structure maintenance during clonal expansion. Like a police on duty, DRAK2 is judiciously crucial for T-cell survival (source).

FREAKY FACT: There is a real vampire community in New Orleans that started in the mid-70s that practices sanguinarian (blood) and psychic feeding – taking energy by physical touch (hands, sexual), astral feeding (mind), or through emotions (source).

DRAK2 -/- promotes positive selection

Despite augmented T-cell activation in the presence of an antagonist, DRAK2−/− mice (all cells are missing the receptor entirely) are resistant to EAE, an autoimmune demyelinating disease that resembles multiple sclerosis (source). The role of DRAK2 in the positive selection for T-cell survival highlights the potential of DRAK2 blockade for the permanent prevention of autoimmune T-cell destruction by intrinsic apoptosis pathway (source).

FREAKY FACT: Physical immortality is not currently available, but transhumanism (H+) – a movement of evolving beyond human limits with biotechnology, nanotechnology, bionics, merging with machines, etc. – increases the potential with every advancement (source).

BONUS EDITION

FREAKY FACT: I performed the role of Renfield in my high school’s production of Bram Stoker’s 1897 novel Dracula. The character was originally a deranged, male asylum patient, but I took artistic license with my role and evolved Renfield into his female counterpart. My Renfield still maintained the propensity for consuming vermin - just with an additional hemorrhage of class fashioned in a burgundy Victorian dress (which I hand-dyed to match the sanguine tone of the story). As someone who tends to be chronically reserved, I was drawn to this socially-accepted outlet for openly exorcising personal demons  that were lurking just beneath my psyche ... and possibly in the shadow of the masses ... (cues ominous music*).

The Tale of Renfield meets the Tale of Drak2

The screenplay Dracula is an examination of insanity from multiple perspectives — the various manifestations, how its perception can be skewed by societal norms, and the power dynamics involved. The original Renfield was forced into an insane asylum after succumbing to his neuroses, and those around found him too abnormal to be around proper society. The administrator of the asylum, Dr. Seward, would create a new category of mental illness for Renfield: "My homicidal maniac is of a peculiar kind. I shall have to invent a new classification for him, and call him a zoophagous (life-eating) maniac” (Stoker 80). Unknowing to those around him, Renfield was actually being manipulated remotely by the predator Count Dracula through mind control, though he was preferred as a slave rather than sustenance as he didn’t pass ”sanity standards.” In tandem, Renfield had an obsession over control — he would consume smaller species and progressively move up the food chain as a way to feel like a “higher being” of power. He believed blood imbued one with powers because his controller fed on it for strength, and thus would express his motives with the Scriptural phrase: “For the blood is the life.”

“My homicidal maniac is of a peculiar kind. I shall have to invent a new classification for him, and call him a zoophagous (life-eating) maniac.”
— Dr. Seward in Bram Stoker's Dracula

DRACULA VS DRAK2

To not give any other spoilers away, I’ll just say that character Renfield may not have been a lead hero to aspire to be per se, and maybe more of a metaphor of the deranged slave that resides in the psyche of the regular Joe(sephine?). However, s(he) also represents the potential that any madman (accused by society or self-proclaimed alike) has for developing rationality when forced to confront one’s humanity in the eyes of another victim. As for the “Tale of Count DRAK2,” parallels in our inner cellular world can be found with our outer turmoil, with the presence of similar factors that make us vulnerable to external circumstances (e.g. UV radiation) to the power dynamics involved in survival (e.g. regulators and effectors). Ultimately, like DRAK2, negative influences may just be necessary for the positive selection of more noble characteristics that push the evolution of mankind. -VF

Dracula (1931): Martin (Charles K. Gerrard) tries to reason with Renfield (Dwight Frye) but his obsession with eating spiders is all-consuming.